Theophylline Sodium Glycinate
Glycine,mixture with 3,7-dihydro-1,3-dimethyl-1H-purine-2,6-dione,monosodium salt.
Theophylline sodium mixture with glycine [8000-10-0]. »Theophylline Sodium Glycinate is an equilibrium mixture containing Theophylline Sodium (C7H7N4NaO2)and Glycine (C2H5NO2)in approximately equimolecular proportions buffered with an additional mole of Glycine.Dried at 105for 4hours,it contains theophylline sodium glycinate equivalent to not less than 44.5percent and not more than 47.3percent of anhydrous theophylline (C7H8N4O2). Packaging and storage— Preserve in tight containers. USP Reference standards á11ñ USP Glycine RS.USP Theophylline RS. Identification— A: Dissolve about 1g in 20mLof warm water,and neutralize the solution with 6Nacetic acid:a white,crystalline precipitate of theophylline is formed.Filter,wash the precipitate with small portions of cold water,and dry it at 105for 1hour:the theophylline so obtained melts between 270and 274,the procedure for Class Ibeing used (see Melting Range or Temperature á741ñ).Retain the remaining portion of the theophylline for use in Identificationtest B. B: Infrared Absorption á197Kñ:residue obtained in Identificationtest A. C: Ignite it:the residue colors a nonluminous flame intensely yellow and effervesces with acids. pHá791ñ: between 8.5and 9.5,in a saturated solution. Loss on drying á731ñ Dry it at 105for 4hours:it loses not more than 2.0%of its weight. Glycine content— Mobile phase— Prepare a solution containing 470mg of sodium acetate trihydrate and 1mLof glacial acetic acid in 2liters of water.Adjust with 10Nsodium hydroxide to a pHof 4.3.Mix 3volumes of the resulting solution with 7volumes of acetonitrile.Make adjustments if necessary (see System Suitabilityunder Chromatography á621ñ). Standard preparation— Dissolve an accurately weighed quantity of USP Glycine RSin Mobile phase,and dilute quantitatively with Mobile phaseto obtain a solution having a known concentration of about 1.3mg per mL. Test preparation— Transfer about 153mg of Theophylline Sodium Glycinate,accurately weighed,to a 50-mLvolumetric flask,dissolve in Mobile phase,dilute with Mobile phaseto volume,and mix. Chromatographic system (see Chromatography á621ñ)—The liquid chromatograph is equipped with a 200-nm detector and a 3.9-mm ×30-cm column that contains packing L8.The flow rate is about 1.5mLper minute.Chromatograph the Standard preparation,and record the peak responses as directed for Procedure:the column efficiency determined from the analyte peak is not less than 2000theoretical plates,the tailing factor for the glycine peak is not more than 2.0,and the relative standard deviation for replicate injections is not more than 2.0%. Procedure— Separately inject equal volumes (about 20µL)of the Standard preparationand the Test preparationinto the chromatograph,record the chromatograms,and measure the responses for the glycine peaks.Calculate the quantity,in mg,of C2H5NO2in the portion of Theophylline Sodium Glycinate taken by the formula: 50C(rU/rS), in which Cis the concentration,in mg per mL,of USP Glycine RSin the Standard preparation,and rUand rSare the peak responses obtained from the Test preparationand the Standard preparation,respectively:not less than 42.0percent and not more than 48.0percent,on the dried basis,is found. Organic volatile impurities,Method Iá467ñ: meets the requirements. Assay— Buffer solution ,Mobile phase,Internal standard solution,Standard preparation,and Chromatographic system—Prepare as directed in the Assayunder Theophylline. Assay preparation— Transfer about 550mg of Theophylline Sodium Glycinate,previously dried and accurately weighed,to a 250-mLvolumetric flask,add about 125mLof Mobile phase,shake by mechanical means until solution is complete,dilute with Mobile phaseto volume,and mix.Transfer 10.0mLof this solution to a 100-mLvolumetric flask,add 20.0mLof Internal standard solution,dilute with Mobile phaseto volume,and mix. Procedure— Proceed as directed for Procedurein the Assayunder Theophylline.Calculate the quantity,in mg,of anhydrous theophylline (C7H8N4O2)in the portion of Theophylline Sodium Glycinate taken by the formula: 2500C(RU/RS), in which the terms are as defined therein. Auxiliary Information— Staff Liaison:Karen A Russo,Ph.D.,Scientist Expert Committee:(PA1)Pharmaceutical Analysis 1 USP28–NF23Page 1902 Phone Number:1-301-816-8379